Status Epilepticus in Our Patients , a 15 Years Follow-Up Study

Introduction: Status epilepticus (SE) is the second most frequent neurological emergency. The purpose of this study was to analyse clinical presentation, causes and outcome of SE. Aim of the Study: The aim was to establish clinical characteristics, etiology and the outcome of status epilepticus as well as sex and age distribution in patients hospitalized at the Clinic of Neurology UCC RS in a 15-year follow-up. Patients and Methods: In this prospective 15-year study, all patients with SE admitted to the University Clinical Center of Republic of Srpska, Clinic of Neurology, were treated in the period of 15 years (2003-2017). Demographic and clinical data were collected. Results: In the aforesaid period, 124 patients with SE were treated, and there were 71 man (57%) with mean age of 59 years and 54 woman (43%), with mean age of 52.5 years. Primarily generalized tonic-clonic SE was identified in 70 (56%) and 44 (35.2%) patients, retrospectively. Simple partial SE occurred in 10 (8%) patients. 62% of the patients had previously had epilepsy while 38% had not. The main underlying causes were noncompliance to treatment in the first group (n=56; 72%) and cerebrovascular disease (n=36; 75%) in the second group. Overall mortality rate was 11.2% , which correlated with acute symptomatic etiology and patients of older age (mean: 73 years). Conclusion: Epileptic patients are at greater risk to develop SE. However, in patients with no prior history of epilepsy and acute neurological problems SE may also occur. Cerebrovascular disease was the most common cause of SE in those with the initial seizure. Noncompliance to treatment was the major cause in patients with preexisting epilepsy.


Introduction
It is usual for status epilepticus not to last long and to have a tendency to spontaneously terminate.It is very rare for individual seizures to last longer than few minutes.However, in some cases, seizures do not terminate spontaneously na their tendency to continue present the essence of status epilepticus.Status epilepticus is the most urgent neurological state and reliability o diagnosis depends on the way the problem is defined. 1,2erall definition indicates that that status epilepticus should be defined as an epileptic activity that is present for 30 minutes or longer as well as the presence of two or more seizures during which the patient does not return to baseline consciousness. 2,3Contemporary papers tend to put under status epilepticus every expressed tendency to repeat epileptic seizures, regardless of their duration and without the full recover of consciousness or other functions affected by the seizure.
Basis for this perception is empirical and is based on the knowledge that epileptic seizures tipically last shorter than few minutes.In greater number of patients, secondary generalized tonic-clonic seizure will last between one and two minutes.Unlike that, most seizures that last longer than 5 minutes will last even longer that 30 minutes if not terminated with the use of medication. 3,4atus epilepticus is a medical and neurological emergency that has been associated with significant morbidity and mortality.SE is a major clinical concern in the adults and specially in the elderly population, both because it has increased incidence in the elderly compared with general population, and because of concurrent medical conditions that are mole likely to complicate therapy and worsen prognosis in elderly individuals. 4,5ny types of epileptic seizures have been described, and, therefore, it follows that there are many types of status epilepticus.This has led to complex classification of status epilepticus.However, using electroclinical features, status epilepticus may be classified simply by the presence of motor convulsions (convulsive status epilepticus) or their absence (nonconvulsive status epilepticus).They may be further divides into status epilepticus that affects the whole brain (generalized status epilepticus) or only part of the brain (partial status epilepticus).Status epilepticus may be initial (first epileptic manifestation) and intercurrent (in patients with prior history of epilepsy). 5

Aim of the Study
The aim was to establish clinical characteristics, etiology and the outcome of status epilepticus as well as sex and age distribution in patients hospitalized at the Clinic of Neurology UCC RS in a 15-year follow-up.

Patients an Methods
In this prospective 15-year study, all patients with SE admitted to the University Clinical Center of Republic of Srpska, Clinic of Neurology, were treated in the period of 15 years (2003-2017).
We also analized demographic data (age, sex), status epilepticus types (generalized tonic-clonic; abans, partial, nonconvulsive, initial or intercurent), outcome of status epilepticus (survived or not), and after the diagnostic procedures, we analysed etiology of status epilepticus.

Results
In the fifteen-years period from 2003-2017.years, we had total of 125 patients with status epilepticus, 71 (57%) of them were male, and 54 (43%) were female.
Mean age of males was 59 years (with the range from 22 to 93 years), while the mean age of females was 52,5 years (with the range from 17 to 93 years).
14 patients died in that period, overall mortality was 11,2%.Deaths were correlated with acute symptomatice etiology due to cerebrovascular disease, and the mean age od those patients was 73 years.
Most of the patients had primarily generalized tonicclonic status epilepticus (n=70; 56%), while the focal onset with secondarily generalized status epilepticus had 44 (35.2%) patients.Simple partial status epilepticus occurred in 10 (8%) patients, and one patient had nonconvulsive status epilepticus (o.8%).An absence of status epilepticus was not registered in our study.
Status epilepticus occurred in 77 (62%) patients with preexisting epilepsy, and in this subgroup of patients, noncompliance to treatment was the major cause in 56 (72%) patients with intercurrent SE.
Status epilepticus occurred in 48 (38%) patients as the first manifestation of disease, and cerebrovascular disease was the main cause in 36 (75%) patients.Etiology of status epilepticus is shown in Table 1.
The most common single cause of status epilepticus in whole group of patients was noncompliance to treatment in patients with preexisting epilepsy in 44.8% patients, followed by cerebrovascular disease in 28.8% patients.The third most common cause of status epilepticus was brain tumors and metastases in 5.6% patients..

SUM: 125 (100)
There is a list of causes with incidence of 4% (alcohol intake, central nervous system infections, febrile systemic infections), followed by causes with the incidence of 2.4% (sequelae of brain injuries and patients with farmacoresistant epilepsy).
As a rare causes of status epilepticus we identified brain injuries and metabolic causes (renal and hepatic encephalopathy) in two patients, and in one patient the etiology remained idiopatic/criptogenic.

Discussion
According to International classification of epilepsy and epileptic syndromes the basic level of recognition of epilepsy and status epilepticus is regarding the etiology.So, we recognise symptomatic, idiopatic and criptogenic status epilepticus.Symptomatic etiologies could be acute or chronic.Idiopatic or criptogenc status epilepticus could have better prognosis than symptomatic ones.7 Criteria for classification depend on anamnesis, undertaken diagnostic procedures, observation and length of follow-up of the patients.Acute symptomatic etiologies correlated with poor outcome. 4To underline the importance of acute symptomatic etiologies, some authors divide all etiologies on acute symptomatic in one hand and all others in another hand. 8 our study, the incidence of status epilepticus was higher for men compared with women (57% vs. 43%).The male patients were older compared with females (59 years vs. 52.5 years).Knake et all. 9and Delanty et all. 11reported in their studies a higher incidence of status epilepticus in men too.Božić et all. 12reported in their study that status epilepticus occurred more often in male patients, and cerebrovascular disease was definitely the predominant cause.
Most of the previous studies suggest acute symptomatic etiology of status epilepticus. 4Hui et.all. 7reported that the most common underlying causes of status epilepticus were cerebrovascular disease, metabolic derangement, anti-convulsant withdrawal and alcohol intake.
Among the patients with status epilepticus as a first epileptic manifestation almost all studies found cerebrovascular disease as a leading underlying cause (Vignatelli et all. 1130%; Afsar et all. 1324.8%;Knake et all. 933%; Darcel et all. 1437%; Delanty et all. 1 41%; Govoni et all. 845%) which correspondents with our results.Amare et all. 15showed in their study with 119 Ethiopian patients that central nervous system infection was the most common cause of status epilepticus in the whole group, as well as in those with new onset seizure.We had 4% of patients with central nervous system infections in our study.
In previous studies, the proportion of patients with preexisting epilepsy was from 46% to 60% 1,9,10,11 and noncompliance to treatment was the major cause for status epilepticus in this group of patients, which correspondents with our results.Di Bonaventura et all. 2 reported that the predominant cause for status epilepticus were noncompliance, withdrawal or reduction of antiepileptc drugs.
In all previous studies, older age and underlying etiology were predictors of mortality.Reported mortalities in previous studies were from 1.9% to 40%. 16 Renal or hepatric encephalopathy are reported in literature as individual causes of status epilepticus. 18,19

Conclusion
Epileptic patients are at greater risk to develop SE.However, in patients with no prior history of epilepsy and acute neurological problems SE may also occur.Cerebrovascular disease was the most common cause of SE in those with the initial seizure.Noncompliance to treatment was the major cause in patients with preexisting epilepsy, which offers a good possibility for prevention.This study confirms the higher incidence of status epilepticus in male patients and in the elderly population.This may be due to a higher incidence of cerebrovascular disease in these subpopulations.Older age and acute symptomatic etiology were the major determinants of death.